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Further Clarifying The Relationship Between Metformin, Acute Kidney Injury And Lactic Acidosis

Further Clarifying The Relationship Between Metformin, Acute Kidney Injury And Lactic Acidosis

Further clarifying the relationship between metformin, acute kidney injury and lactic acidosis Subscribe to Nature Reviews Nephrology for full access: Diabetes mellitus: complex interplay between metformin, AKI and lactic acidosis Bell, S., Soto-Pedre, E., Connelly, P., Livingstone, S. & Pearson, E. Clarifying the relationship between metformin, acute kidney injury and lactic acidosis . Nat. Rev. Nephrol. , (2017). Rhee, C. M., Kovesdy, C. P. & Kalantar-Zadeh, K. Risks of metformin in type 2 diabetes and chronic kidney disease: lessons learned from Taiwanese data Risk of acute kidney injury and survival in patients treated with metformin: an observational cohort study Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: a GoDarts study . Diabetes Obes. Metab. 19, 1579–1586 (2017). Inzucchi, S. E., Lipska, K. J., Mayo, H., Bailey, C. J. & McGuire, D. K. Metformin in patients with type 2 diabetes and kidney disease: a systematic review Restricting metformin in CKD: continued caution warranted . Am. J. Kidney Dis. 66, 1101–1102 (2015). Should restrictions be relaxed for metformin use in chronic kidney disease? Yes, they should be relaxed! What's the fuss? Should restrictions be relaxed for metformin use in chronic kidney disease? No, we should never again compromise safety! Metformin in chronic kidney disease: more harm than help? Lancet Diabetes Endocrinol. 3, 579–581 (2015). Metformin use in type 2 diabetes mellitus With CKD: is it time to liberalize dosing recommendations? Kalantar-Zadeh, K., Uppot, R. N. & Lewandrowski, K. B. Case records of the Massachusetts General Hospital. Case 23–2013. A 54-year-old woman with abdominal pain, vomiting, and confusion United States Renal Data System. USRDS 2017 Annual Data Report: Atlas Continue reading >>

Should Metformin Use In Patients With Chronic Kidney Disease Be Expanded?

Should Metformin Use In Patients With Chronic Kidney Disease Be Expanded?

Should Metformin Use In Patients With Chronic Kidney Disease Be Expanded? Medical Director, Unger Primary Care Medicine Group, Rancho Cucamonga, CA Dr. Unger reports no financial relationships relevant to this field of study. SYNOPSIS: Expansion of the metformin label to include patients with mild-to-moderate kidney disease is appropriate. SOURCE: Inzucchi SE, et al. Metformin in patients with type 2 diabetes and kidney disease. A systematic review. JAMA 2014;312: There were 818 manuscripts published between 1950 and June 2014 that were reviewed from MEDLINE and Cochrane database pertaining to metformin, kidney disease, and lactic acidosis. Although metformin is renally cleared, drug levels generally remain within therapeutic range and lactate concentrations are not substantially increased in patients with estimated glomerular filtration rates of 30-60 mL/min per 1.73 m2. The overall incidence of lactic acidosis in metformin users varies across studies from 3 per 100,000 patient years to 10 per 100,000 patient years, which is indistinguishable from the non-diabetic population. No randomized, controlled trials have been conducted to test the safety and efficacy of metformin in patients with severely impaired renal function (eGFR < 30 mL/min per 1.73 m2). Expansion of the metformin label to include patients with mild-to-moderate kidney disease is appropriate. (See Table 2.) Metformin was initially approved by the FDA for use in type 2 diabetes in 1994. The drug is widely accepted as the foundation of care for patients with type 2 diabetes based on its low cost, safety profile, potential cardiovascular benefits, and likelihood of reducing cancer risk in some patients. Another biguanide, phenformin, was withdrawn in 1977 due to a risk of lactic acidosis. Metformin is renal Continue reading >>

Metformin Appears Safe For Patients With Mild To Moderate Ckd

Metformin Appears Safe For Patients With Mild To Moderate Ckd

Metformin appears safe for patients with mild to moderate CKD Inzucchi SE. JAMA. 2014;doi:10.1001/jama.2014.15298. Clinicians may expand the use of metformin in patients with type 2 diabetes with mild to moderate kidney disease cautiously, based on literature showing limited evidence of increased risk for lactic acidosis, according to a review published in JAMA. Our systematic review found that the actual risk of lactic acidosis in metformin-treated patients is essentially equivalent to the background rate in patents whose type 2 diabetes is being treated with other drugs, Silvio E. Inzucchi, MD, of Yale University School of Medicine, told Endocrine Today. Moreover, in the rare circumstance where a metformin-treated patient does develop lactic acidosis, there is usually another explanation for the metabolic decompensation. The data suggest that the drug can be continued when estimated glomerular filtration rates drop below 60mL/min/1.73 m2, Inzucchi said. WheneGFR reaches 45mL/min/1.73 m2, the dose should be reduced by half and stopped when eGFR reaches 30mL/min/1.73 m2. These recommendations are similar to those already in widespread use intheUnited Kingdom, Inzucchi said. He and colleagues searched MEDLINE and Cochrane databases for articles published between 1950 and 2014 pertaining to metformin, kidney disease and lactic acidosis. The researchers included 65 articles, of 818 initially identified, comprising pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses and a clinical trial. The investigators found that metformin levels generally remain in the therapeutic range, with lactate concentrations not considerably increased, when used in patients with mild to moderate CKD (30-60 mL/min per 1.73m2). Overall incidence of lactic aci Continue reading >>

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Risks Of Metformin In Type 2 Diabetes And Chronic Kidney Disease: Lessons Learned From Taiwanese Data

Abstract Like other biguanide agents, metformin is an anti-hyperglycemic agent with lower tendency towards hypoglycemia compared to other anti-diabetic drugs. Given its favorable effects on serum lipids, obese body habitus, cardiovascular disease, and mortality, metformin is recommended as the first-line pharmacologic agent for type 2 diabetes in the absence of contraindications. However, as metformin accumulation may lead to type B non-hypoxemic lactic acidosis, especially in the setting of kidney injury, chronic kidney disease, and overdose, regulatory agencies such as the United States Food and Drug Administration (FDA) have maintained certain restrictions regarding its use in kidney dysfunction. Case series have demonstrated a high fatality rate with metformin-associated lactic acidosis (MALA), and the real-life incidence of MALA may be underestimated by observational studies and clinical trials that have excluded patients with moderate-to-advanced kidney dysfunction. A recent study of advanced diabetic kidney disease patients in Taiwan in Lancet Endocrinology and Diabetes has provided unique insight into the potential consequences of unrestricted metformin use, including a 35% higher adjusted mortality risk that was dose-dependent. This timely study, as well as historical data documenting the toxicities of other biguanides, phenformin and buformin, suggest that the recent relaxation of FDA recommendations to expand metformin use in patients with kidney dysfunction (i.e., those with estimated glomerular filtration rates ≥30 instead of our recommended ≥45 ml/min/1.73 m2) may be too liberal. In this article, we will review the history of metformin use; its pharmacology, mechanism of action, and potential toxicities; and policy-level changes in its use over time. Continue reading >>

Should Fda Change Metformin's Black Box Warning?

Should Fda Change Metformin's Black Box Warning?

Diabetes experts are building a case to lift restrictions on using metformin in patients with moderate chronic kidney disease. Two groups of researchers who have separately filed citizens petitions with the FDA have published studies in JAMA journals in the past few weeks showing a lack of evidence for metformin-associated lactic acidosis -- a severe complication that prompted the FDA to warn against the drug's use in CKD patients when it came on the market 20 years ago. Silvio Inzucchi, MD, and Kasia Lipska, MD, MHS, of Yale, published a review in the Dec. 24/31 issue of JAMA concluding that most observational data -- there are no randomized controlled trials -- confirm the "overall safety profile" of metformin in mild-to-moderate CKD patients. And James Flory, MD, of Weill Cornell, and Sean Hennessy, PharmD, PhD, of the University of Pennsylvania, reported in a research letter in the Jan. 5 issue of the Archives of Internal Medicine, that nearly 1 million patients who have diabetes and CKD could be taking metformin but aren't. Both groups have asked the FDA to lift its black box warning that limits prescribing in CKD patients based on serum creatinine levels (1.5 mg/dL or above for men, 1.4 mg/dL for women), and asks the agency to use eGFR cutoffs instead -- typically, at 30 mL/min, where several professional societies and other international regulators draw the line. How the Black Box Came to Be When the FDA approved metformin in 1994, it slapped on the black box warning about lactic acidosis because of a similar problem with another biguanide, phenformin. This cousin to metformin was withdrawn from the market in 1977 because of an increased risk of lactic acidosis. Since metformin is also renally cleared, the agency was concerned that metabolism of the drug could co Continue reading >>

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Clinical Outcomes Of Metformin Use In Populations With Chronic Kidney Disease, Congestive Heart Failure, Or Chronic Liver Disease: A Systematic Review

Abstract Background: Recent changes to the U.S. Food and Drug Administration boxed warning for metformin will increase its use in persons with historical contraindications or precautions. Prescribers must understand the clinical outcomes of metformin use in these populations. Purpose: To synthesize data addressing outcomes of metformin use in populations with type 2 diabetes and moderate to severe chronic kidney disease (CKD), congestive heart failure (CHF), or chronic liver disease (CLD) with hepatic impairment. Data Sources: MEDLINE (via PubMed) from January 1994 to September 2016, and Cochrane Library, EMBASE, and International Pharmaceutical Abstracts from January 1994 to November 2015. Study Selection: English-language studies that: 1) examined adults with type 2 diabetes and CKD (with estimated glomerular filtration rate less than 60 mL/min/1.73 m2), CHF, or CLD with hepatic impairment; 2) compared diabetes regimens that included metformin with those that did not; and 3) reported all-cause mortality, major adverse cardiovascular events, and other outcomes of interest. Data Extraction: 2 reviewers abstracted data and independently rated study quality and strength of evidence. Data Synthesis: On the basis of quantitative and qualitative syntheses involving 17 observational studies, metformin use is associated with reduced all-cause mortality in patients with CKD, CHF, or CLD with hepatic impairment, and with fewer heart failure readmissions in patients with CKD or CHF. Limitations: Strength of evidence was low, and data on multiple outcomes of interest were sparse. Available studies were observational and varied in follow-up duration. Conclusion: Metformin use in patients with moderate CKD, CHF, or CLD with hepatic impairment is associated with improvements in key c Continue reading >>

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Clinical Research Extending Metformin Use In Diabetic Kidney Disease: A Pharmacokinetic Study In Stage 4 Diabetic Nephropathy

Metformin use in advanced chronic kidney disease is controversial. This study sought to examine the pharmacokinetics, safety, and efficacy of low-dose metformin in patients with type 2 diabetes and stage 4 chronic kidney disease. In this open-label, phase I trial, 3 consecutive cohorts (1, 2, and 3) of 6 patients each were recruited to receive 250-, 500-, or 1000-mg once-daily doses of metformin, respectively. All patients underwent a first-dose pharmacokinetic profile and weekly trough metformin concentrations for the duration of 4 weeks of daily therapy. Prespecified clinical and biochemical safety endpoints of serum bicarbonate, venous pH, and serum lactate were assessed weekly. Efficacy was assessed by pre- and post-HbA1c and 72-hour capillary glucose monitoring. There was no evidence of accumulation of metformin in any cohort. There were no episodes of hyperlactatemia or metabolic acidosis and no significant change in any biochemical safety measures. Median (interquartile range) observed trough concentrations of metformin in cohorts 1, 2, and 3 were 0.083 (0.121) mg/l, 0.239 (0.603) mg/l, and 1.930 (3.110) mg/l, respectively. Average capillary glucose concentrations and mean HbA1c decreased in all cohorts. In our patient cohorts with diabetes and stage 4 chronic kidney disease, treatment with 4 weeks of low-dose metformin was not associated with adverse safety outcomes and revealed stable pharmacokinetics. Our study supports the liberalization of metformin use in this population and supports the use of metformin assays for more individualized dosing. Figure 2. Safety profile (venous lactate, bicarbonate, and pH) in all 3 cohorts across the study period. Venous lactate for patient 11 appears as a dotted line. Patients 2 and 19 commenced metformin therapy a few days Continue reading >>

Metformin In Patients With Type 2 Diabetes And Kidney Disease

Metformin In Patients With Type 2 Diabetes And Kidney Disease

Go to: Abstract Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies d Continue reading >>

Metformin Challenges In Advanced Chronic Kidney Disease: A Promising Therapeutic Strategy

Metformin Challenges In Advanced Chronic Kidney Disease: A Promising Therapeutic Strategy

Metformin Challenges in Advanced Chronic Kidney Disease: A Promising Therapeutic Strategy M. Fidalgo Daz * , R. Alonso Valente, V. Becerra Mosquera, I. Abuward, S. Puello Martnez, N. Ardha, M. Durn Beloso, D. Novoa Garca, T. Cordal Martnez, D. Gimil Carbajal, C. Daz Rodrguez Department of Nephrology, Hospital Clnico Universitario de Santiago de Compostela, Spain Received Date: July 12, 2017; Accepted Date: August 16, 2017; Published Date: August 18, 2017 Citation: Daz MF, Valente RA, Mosquera VB, Abuward I, Martnez SP, et al. (2017) Metformin Metformin Challenges in Advanced Chronic Kidney Disease. A Promising Therapeutic Strategy. Jour Ren Med. Vol.1 No.2: 12. Visit for more related articles at Journal of Renal Medicine Background: Metformin is the first-line treatment in type 2 diabetes mellitus because the beneficial effects respect to other antidiabetic drugs on hypoglycemia, obesity, dyslipidemia and cardiovascular morbidity and mortality and even on renal cancer incidence. However, the accumulation of metformin in cases of impaired renal function may lead to a type B lactic acidosis, which has led to its contraindication in patients with chronic kidney disease (CKD), initially to glomerular filtration less than 60 ml/min and subsequently less than 30 ml/min. The dosedependent toxicity, the low rate of onset of metforminassociated lactic acidosis (MALA) and lack of knowledge of pharmacokinetics in CKD, have motivated the development of studies which could support metformin use in advanced stages of CKD. Methods: We did a literature review compiling recent, more relevant and impact articles, to conclude about the current situation of metformin safety in advanced stages of CKD as well as try to offer a concise future perspective. The analysis has been structured abo Continue reading >>

Metformin In Advanced Chronic Kidney Disease: Are Current Guidelines Overly Restrictive?

Metformin In Advanced Chronic Kidney Disease: Are Current Guidelines Overly Restrictive?

Abstract Type 2 diabetes mellitus and chronic kidney disease (CKD) frequently co-exist and the increasing burden of both conditions is a global concern. Metformin is established as the first-line treatment for type 2 diabetes because it is associated with improved cardiovascular outcomes and a reduced risk of hypoglycaemia compared with other treatment options. Patients with CKD may benefit in particular because they are at high risk of both cardiovascular disease and hypoglycaemic episodes. However, the use of metformin is restricted in this population due to the concerns over lactic acidosis. Recent reviews have evaluated this risk and concluded that current guidelines for prescribing metformin in CKD may be too restrictive. This narrative review considers this evidence further, but also examines the strength of evidence that favours the use of metformin in CKD patients. Discover the world's research 14+ million members 100+ million publications 700k+ research projects Join for free tions is a global concern. Metformin is established as the ing dialysis in the UK, with an incidence of 25.4%.2Overt diabetic The International Diabetes Federation (IDF) estimates that 387 References for this review were identified through searches of 7.0% (53 mmol/mol) in the intensive group and 7.9% (63 diabetes to undergo standard glucose control (mean HbA1c minuria. There was a significantly lower incidence of major the incidence of nephropathy. The use of most classes of oral risk of developing ESRD (65%), microalbuminuria (9%) and They state that its use is contraindicated with a creatinine >1.5 mg/dL (133 μmol/L) in men or >1.4 mg/dL (124 μmol/L) in the prevalence of people with an eGFR of <45 mL/min was the large burden of type 2 diabetes, these data suggest that randomisation op Continue reading >>

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

ADVANTAGES OF METFORMIN There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% (P = 0.010) risk reduction for myocardial infarction and a 36% reduction for total mortality (P = 0.011) compared with conventional diet treatment. Similar benefits were not observed in those randomly assigned to sulfonylurea or insulin. In an 8.5-year posttrial monitoring study, after participants no longer were randomly assigned to their treatments, individuals originally assigned to metformin (n = 279) continued to demonstrate a reduced risk for both myocardial infarction (relative risk 33%, P = 0.005) and total mortality (relative risk 27%, P = 0.002) (9). The latter results are even more impressive when one considers that HbA1c levels in all initially randomly assigned groups had converged within 1 year of follow-up. Unlike sulfonylureas, thiazolidinediones, and insulin, metformin is weight neutral (10), which makes it an attractive choice for obese patients. Furthermore, the management of type 2 diabetes can be complicated by hypoglycemia, which can seriously limit the pursuit of glycemic control. Here, too, metformin has advantages over insulin and some Continue reading >>

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As you were browsing PracticeUpdate, something about your browser made us think you were a bot. There are a few reasons this might happen: You're a power user moving through this website with super-human speed. You've disabled JavaScript in your web browser. A third-party browser plugin, such as Ghostery or NoScript, is preventing JavaScript from running. Additional information is available in this . After completing the CAPTCHA below, you will immediately regain access to PracticeUpdate. ​ You reached this page when attempting to access from 35.226.183.143 on 2018-01-06 18:18:13 UTC. Trace: 8d3497e3-c874-476e-b444-70710053403c via f142fe30-0da7-428a-92b2-8a74e399b4ec Continue reading >>

Metformin In Patients With Type 2 Diabetes And Kidney Disease: A Systematic Review.

Metformin In Patients With Type 2 Diabetes And Kidney Disease: A Systematic Review.

JAMA. 2014 Dec 24-31;312(24):2668-75. doi: 10.1001/jama.2014.15298. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut. Health Sciences Digital Library and Learning Center, University of Texas Southwestern Medical Center, Dallas. School of Life & Health Sciences, Aston University, Birmingham, United Kingdom. Division of Cardiology, University of Texas Southwestern Medical Center, Dallas. Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users v Continue reading >>

Primary Care Corner With Geoffrey Modest Md: Metformin In Renal Failure

Primary Care Corner With Geoffrey Modest Md: Metformin In Renal Failure

Primary Care Corner with Geoffrey Modest MD: Metformin in renal failure JAMA just published a systematic review of the literature on the use of metformin in patients with chronic kidney disease(seeJAMA. 2014;312(24):2668-2675). The major concern is that metformin is renally-cleared, and that its close cousin, phenformin, was used extensively in the US, caused large numbers of cases of fatal lactic acidosis and was pulled off the market in 1977.Major points from the systematic review: 65 studies identified, mostly case series and observational post-marketing surveillance but also some pharmacokinetic/metabolic ones though there is reduced metformin clearance with renal insufficiency,both metformin andlactic acid levels are in safe rangesin patients with eGFR of 30-60 mL/min/1.73m2 the incidence of lactic acidosis in metformin users is 3-10/100K person-years, generally indistinguishable from the background rate. For example,an analysis of 347 studies of diabetics found no cases of lactic acidosis in 70,490 patient-years on metformin (nor in 55,451 in those not on metformin). small studies which have reported metformin lactic acidosis have typically been in hospitalized patients with supervening illnesses precipitating metabolic decompensation (eg infection, acute kidney/liver failure, cardiovasc collapse). Unclear if the lactic acidosis wasrelated to metformin. When metformin levels weremeasured, they were occasionally elevated but no consistent correlation with the lactic acidosis. observational studies suggest macrovascular benefit of metformin in patients with renal insufficiency. For example, a study of 19,691 diabeticpatients with atherosclerotic disease found that mortality rates were 6.3% in those on metformin but 9.8% in those not. this benefit persisted in the s Continue reading >>

Changes In Metformin Use In Chronic Kidney Disease

Changes In Metformin Use In Chronic Kidney Disease

Background Glucose-lowering biguanides were discovered in the 1920s. One of these was metformin (dimethylbiguanide), but it was then forgotten [1]. The first human trial on biguanides that used the name Glucophage (glucose eater) was published in 1957 [2]. In the next couple of years reports were published on phenformin [3] and buformin [4]. However, due to their association with lactic acidosis (LA), both phenformin and buformin were withdrawn from many countries. Similar concerns were raised for metformin, but it remained on the market and has been available in the UK since 1958, although it only became available in the USA in 1994. Clinical benefits in diabetes mellitus type 2 Metformin acts primarily in the liver by reducing glucose output and also by enhancing peripheral uptake of glucose, mainly in muscles. It is not generally associated with a risk of hypoglycemia unless there is excessive exercise, severe calorie reduction or when mixed with other antidiabetic medicine. There is absence of weight gain along with modest reductions in triglycerides [5]. It causes a reduction in mortality by decreasing cardiovascular complications [6]. Metformin has shown some effectiveness in polycystic ovarian syndrome, some gynecological cancers, nonalcoholic fatty liver disease and for premature puberty. However, its main role remains in the management of diabetes mellitus type 2 (DM2). The International Diabetes Federation lists it as one of the first antidiabetic medicines to be used for DM2 [7]. The World Health Organization lists it as one of two essential medicines for diabetes [8]. Fear of LA Metformin is chemically similar to phenformin, but has a different mechanism of action. Although the fear of LA remains, no absolute definitive causal relationship has been proven be Continue reading >>

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